Dalhousie Inflammation Group, Dalhousie University, Halifax, Nova Scotia, Canada.
Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
Immun Inflamm Dis. 2018 Mar;6(1):176-189. doi: 10.1002/iid3.211. Epub 2017 Dec 13.
Mast cells are resident immune effector cells, often studied in the context of allergic disease. Found in substantial numbers at sites of potential infection they are increased at sites of angiogenesis and can be pivotal for the sensing and clearance of a variety of pathogens. Interferons (IFNs) are cytokines that are critical for host defence against intracellular pathogens. Increased levels of IFNs are observed during viral infection and in autoimmune diseases. IFNs are also widely used therapeutically and have been examined in the therapy of severe asthma.
To define the selective human mast cell cytokine and chemokine response following activation with type I or type II IFN's.
The ability of both IFNα2 and IFNγ to induce cytokine production by human cord blood-derived mast cells was examined in vitro. Cytokine and chemokine production at 6 and 24 h was assessed by multiplex protein analysis. Degranulation was assessed by β-hexosaminidase release. Mast cells were also treated with reovirus or respiratory syncytial virus and their production of CXCL10, IL-1 receptor antagonist (IL-1Ra), and vascular endothelial growth factor (VEGF) examined after 24 h.
In addition to increased expression of classical IFN response genes, such as CXCL10, small but significant increases in CCL5 and IL-17 production were observed following IFN activation. Notably, human mast cells produced both VEGF and IL-1Ra in a dose dependent manner. These responses occurred in the absence of mast cell degranulation by a mechanism consistent with classical IFN signaling. Both reovirus and respiratory syncytial virus infection of mast cells, were also associated with IFN-dependent IL-1Ra expression.
Our findings demonstrate that IFNs have profound impact on cytokine and chemokine expression by human mast cells, alone or in the context of viral infection. Mast cell VEGF and IL-1Ra responses to IFNs could impact the regulation of local inflammatory responses and subsequent tissue remodeling.
肥大细胞是常驻免疫效应细胞，常被研究在过敏疾病的背景下。它们在潜在感染部位大量存在，在血管生成部位增加，对各种病原体的感知和清除起着关键作用。干扰素（IFN）是细胞因子，对宿主抵抗细胞内病原体至关重要。在病毒感染和自身免疫性疾病中观察到 IFN 水平升高。IFN 也被广泛用于治疗，并在严重哮喘的治疗中进行了研究。
定义 I 型或 II 型 IFN 激活后选择性的人肥大细胞细胞因子和趋化因子反应。
在体外研究了 IFNα2 和 IFNγ 诱导人脐带血衍生肥大细胞产生细胞因子的能力。通过多重蛋白质分析评估 6 和 24 小时的细胞因子和趋化因子产生。通过β-己糖胺酶释放评估脱颗粒。还用呼肠孤病毒或呼吸道合胞病毒处理肥大细胞，并在 24 小时后检查 CXCL10、白细胞介素 1 受体拮抗剂（IL-1Ra）和血管内皮生长因子（VEGF）的产生。
除了经典 IFN 反应基因（如 CXCL10）的表达增加外，IFN 激活后还观察到 CCL5 和 IL-17 产生的小但显著增加。值得注意的是，人肥大细胞以剂量依赖的方式产生 VEGF 和 IL-1Ra。这些反应是在肥大细胞脱颗粒的情况下发生的，机制与经典 IFN 信号一致。肥大细胞感染呼肠孤病毒和呼吸道合胞病毒也与 IFN 依赖性 IL-1Ra 表达有关。
我们的研究结果表明，IFN 对人肥大细胞的细胞因子和趋化因子表达具有深远的影响，无论是单独作用还是在病毒感染的情况下。IFN 对肥大细胞 VEGF 和 IL-1Ra 的反应可能会影响局部炎症反应的调节和随后的组织重塑。
